HbA1c Assay Methodologies and Proficiency Testing: Ensuring Accuracy in Diabetes Management

Accurate glycemic-monitoring and control of the patients with hyperglycemia/diabetes are essential for better patient care management. Hemoglobin A1c (HbA1c) measurements correlate with the average plasma glucose level over the preceding 2-3 months. HbA1c is a stable, glycated hemoglobin formed by non-enzymatic addition of glucose to amino-terminal end of Hb polypeptide chains. HbA1c is stable through the life of red blood cells (RBCs) and can be measured regardless of the time of the day and fasting status. Therefore, HbA1c testing has become the standard of practice for glycemic control assessment. According to the American Diabetes Association (ADA) guidelines, through National Glycohemoglobin Standardization Program (NGSP)-certified Diabetes Control and Complications Trial (DCCT)-standardized assay, an HbA1c level between 5.7% and 6.4% is defined as prediabetes, and a level of 6.5% or more is consistent for diagnosis of diabetes. Hemoglobin (Hb) variants arise due to mutations causing changes in Hb alpha or beta chain aminoacid at a particular sequence. Many methodologies are available for HbA1c testing some of which can affect the results based on Hb variant. In this session, principles of HbA1c assays such as ion-exchange high-performance liquid chromatography (HPLC), boronate affinity HPLC, capillary electrophoresis, immunoassay and enzymatic assays will be explained. The analytical and biological limitations of these assays-such as hemoglobinopathies (Hb variants) will be discussed and compared. In addition, details surrounding CAP proficiency testing (PT) limits, CLIA rule and the efforts of NGSP related to HbA1c testing improvement will be presented.

Learning Objectives:

• Understand the background of diabetes and importance of HbA1c for diabetes monitoring
• Review various methodologies and best practices for HbA1c Testing
• Evaluate role of NGSP and CAP Proficiency Testing Program for HbA1c